The restoration of visual function is one of the ultimate aims in vision research. Present treatments for severe diseases leading to blindness, such as age related macular degeneration (AMD), glaucoma, diabetic retinopathy and complications of retinal detachment, are only supportive or slow down disease progression, but do not restore visual function. Recent research involving stem cell transplantation in a wide disease spectrum has triggered enthusiasm across the medical and scientific community, and stem cell research to restore neural circuits in diseased retinas are encouraged by results obtained with progenitor cell transplantation to treat other human diseases, including leukemia, severe skin burns and myocardial disfunction.
To date, transplantation studies aimed at restoration of human retinal function have yielded little success, and have been limited to transplantation of retinal pigment epithelial (RPE) and Iris pigment epithelial (IPE) cells. Experimental transplantation of RPE, Schwann and brain-derived pre-cursor cells in animal models of retinal degeneration has provided some success in the preservation of retinal function. Retinal transplantation of brain-derived precursor cells to RCS rats (a model of retinal degeneration) promotes photoreceptor cell survival. However, although the transplanted cells migrate to the photoreceptor cell layer, they fail to express retinal neural markers, suggesting that a specific neuronal precursor is needed for functional and morphological regeneration of the retina.
During early studies, it was thought that stem cells could only be isolated from embryos, for which neural progenitors were first identified in the embryonic mammalian central system and peripheral nervous system (CNS and PNS). However, more recent investigations have identified adult stem cells in neurogenic regions of the CNS, and this has prompted further investigations in the search for adult stem cells.
Limb et al., IOVS, 2002; 43(3); 864-869 discloses the identification of a spontaneously immortalised Müller cells.
Müller cells are radial glial cells that extend vertically through the whole width of the retina. They stabilise the complex retinal architecture, give structural and metabolic support to neurons and blood vessels, prevent aberrant photoreceptor migration into the sub-retinal space and regulate fluid transport between the vitreous cavity and the sub-retinal space. Nearly all retinal pathological conditions that constitute major causes of blindness, including age related macular degeneration, proliferative diabetic retinopathy, proliferative vitreoretinopathy (PVR) and retinitis pigmentosa (RP), are associated with changes in Müller cell distribution, proliferation or function.
Fischer et al., Nature Neuroscience, 2001; 4(3): 247-252 describes the identification of Müller glial cells obtained from the retina of post-natal chicken. The Müller glial cells are shown to be non-differentiated, proliferate and express transcription factors normally expressed by embryonic retinal progenitors. The Müller glial cells proliferate in response to retinal damage.
In the human eye, it has been shown that Müller stem cells given origin to various retinal cells are found during foetal development, but no evidence has yet been shown that these cells may be present in the adult neural retina. There is therefore a need to develop cells suitable for use in retinal cell transplantation therapies, for the treatment of human retinal damage.